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Human Medicine (human + medicine)
Selected AbstractsStatistical issues in first-in-man studiesJOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES A (STATISTICS IN SOCIETY), Issue 3 2007Professor Stephen Senn Preface., In March 2006 a first-in-man trial took place using healthy volunteers involving the use of monoclonal antibodies. Within hours the subjects had suffered such adverse effects that they were admitted to intensive care at Northwick Park Hospital. In April 2006 the Secretary of State for Health announced the appointment of Professor (now Sir) Gordon Duff, who chairs the UK's Commission on Human Medicines, to chair a scientific expert group on phase 1 clinical trials. The group reported on December 7th, 2006 (Expert Scientific Group on Clinical Trials, 2006a). Clinical trials have a well-established regulatory basis both in the UK and worldwide. Trials have to be approved by the regulatory authority and are subject to a detailed protocol concerning, among other things, the study design and statistical analyses that will form the basis of the evaluation. In fact, a cornerstone of the regulatory framework is the statistical theory and methods that underpin clinical trials. As a result, the Royal Statistical Society established an expert group of its own to look in detail at the statistical issues that might be relevant to first-in-man studies. The group mainly comprised senior Fellows of the Society who had expert knowledge of the theory and application of statistics in clinical trials. However, the group also included an expert immunologist and clinicians to ensure that the interface between statistics and clinical disciplines was not overlooked. In addition, expert representation was sought from Statisticians in the Pharmaceutical Industry (PSI), an organization with which the Royal Statistical Society has very close links. The output from the Society's expert group is contained in this report. It makes a number of recommendations directed towards the statistical aspects of clinical trials. As such it complements the report by Professor Duff's group and will, I trust, contribute to a safer framework for first-in-man trials in the future. Tim Holt (President, Royal Statistical Society) [source] Latest news and product developmentsPRESCRIBER, Issue 8 2008Article first published online: 12 MAY 200 Glargine preferred to lispro as type 2 add-on Basal insulin glargine (Lantus) and insulin lispro (Humalog) at mealtimes improved glycaemic control equally well in patients with type 2 diabetes poorly controlled by oral agents, but patient satisfaction was greater with basal insulin (Lancet 2008;371:1073-84). The 44-week APOLLO trial, funded by Sanofi Aventis, was a nonblinded randomised comparison of basal and prandial insulin regimens added to oral treatment in 418 patients. It found similar reductions in HbA1C (,1.7 vs ,1.9 per cent respectively). Fasting and nocturnal glucose levels were lower with insulin glargine and postprandial levels were lower with insulin lispro. The basal regimen was associated with fewer hypoglycaemic events (5.2 vs 24 per patient per year), less weight gain (3.01 vs 3.54kg) and greater improvement in patient satisfaction scores. Treating hypertension cuts mortality in over-80s Treating hypertension in the over-80s reduces all-cause mortality by 21 per cent, the HYVET study has shown (N Engl J Med online: 31 March 2008; doi: 10.1056/NEJMoa 0801369). Compared with placebo, treatment with indapamide alone or with perindopril for an average of 1.8 years also reduced the incidence of fatal stroke by 39 per cent, cardiovascular death by 23 per cent and heart failure by 64 per cent. The incidence of stroke was reduced by 30 per cent but this was of borderline statistical significance. Fewer serious adverse events were reported with treatment than with placebo. New work for NICE The DoH has announced the 18th work programme for NICE. Seven public health interventions include preventing skin cancer, smoking by children and excess weight gain during pregnancy. Public health guidance will include the provision of contraceptive services for socially disadvantaged young people. Two new clinical guidelines are sedation in young people and management of fractured neck of femur. New technology appraisals may include eight therapies for cancer, two new monoclonal antibodies for psoriasis and rheumatoid arthritis, an oral retinoid for severe chronic hand eczema and methylnaltrexone for opioid-induced bowel dysfunction. Combinations no better against CV disease Taking ezetimibe and simvastatin (Inegy) does not appear to slow the progression of atherosclerosis more than high-dose simvastatin alone, say researchers from The Netherlands (N Engl J Med 2008;358: 1431-43). In patients with hypercholesterolaemia, there was no difference in regression or progression of atherosclerosis after two years' treatment with simvastatin 80mg per day alone or combined with ezetimibe 10mg per day. Adverse event rates were similar. In patients with vascular disease or high-risk diabetes, there was no difference between the ACE inhibitor ramipril 10mg per day or the ARB telmisartan (Micardis) 80mg per day as monotherapy, or their combination, in the risk of a composite outcome of cardiovascular death, MI, stroke and admission for heart failure (N Engl J Med 2008;358:1547-59). Combined treatment was associated with higher risks of hypotensive symptoms, syncope and renal dysfunction. Twice-daily celecoxib increases CV risk Taking celecoxib (Celebrex) twice daily carries a higher risk of cardiovascular events than the same total dose taken once daily, a metaanalysis suggests (Circulation 2008; doi: 10.1161/ CIRCULATIONAHA.108. 764530). The analysis of six placebo-controlled trials involving a total of 7950 patients taking celecoxib for indications other than rheumatoid arthritis found that the combined risk of cardiovascular death, myocardial infarction, stroke, heart failure or thromboembolic event increased with dose over the range 400-800mg per day. The risk was significantly greater with 200mg twice daily (HR 1.8) than 400mg once daily (HR 1.1). Patients at greatest baseline risk were at disproportionately increased risk from celecoxib. Long-term etanercept effective in AS An open-label study suggests that etanercept (Enbrel) remains effective in the treatment of ankylosing spondylitis in the long term (Ann Rheum Dis 2008;67:346-52). Of 257 patients who completed six months' treatment with etanercept and who entered the nonblinded extension study, 126 completed a total of 168-192 weeks' treatment. The commonest adverse events were injection-site reactions (22 per cent), headache (20 per cent) and diarrhoea (17.5 per cent). The annual rate of serious infections was 0.02 per person. Response and partial remission rates after 192 weeks were similar to those reported after 96 weeks. Metformin reduces risk Metformin reduces the risk of developing diabetes in individuals at increased risk, a meta-analysis suggests (Am J Med 2008;121:149-57.e2). The study included 31 mostly small, randomised, controlled trials involving a total of 4570 participants and lasting at least eight weeks (8267 patient-years of treatment). Metformin was associated with reductions in body mass (,5.3 per cent), fasting glucose (,4.5 per cent) and insulin resistance (,22.6 per cent); lipid profiles also improved. The odds of developing diabetes were reduced by 40 per cent,an absolute risk reduction of 6 per cent over 1.8 years. MHRA clarifies cough and colds advice Press reports mistakenly suggested that the MHRA had banned some cough and cold remedies when it issued new guidance on treating young children, the MHRA says. The Agency's advice followed a review of over-thecounter cough and cold medicines for children by the Commission on Human Medicines. Children under two are at increased risk of adverse reactions and should no longer be treated with products containing antihistamine (chlorphenamine, brompheniramine, diphenhydramine), antitussives (dextromethorphan, pholcodine), expectorants (guaifenesin, ipecacuanha) and decongestants (phenylephrine, pseudoephedrine, ephedrine, oxymetazoline and xylometazoline). The MHRA said these products, which are classified as general sale medicines, should be removed from open shelves until available in new packaging that complies with the advice. They may still be supplied by a pharmacist for the treatment of older children. Coughs and colds should be treated with paracetamol or ibuprofen for fever, a simple glycerol, honey or lemon syrup for cough, and vapour rubs and inhalant decongestants for stuffy nose. Saline drops can be used to thin and clear nasal secretions in young babies. Parents are being urged not to use more than one product at a time to avoid inadvertently administering the same constituent drug twice. Perindopril brand switch Servier Laboratories is replacing its current formulations of perindopril (Coversyl, Coversyl Plus) with a new product that is not bioequivalent. The current Coversyl brand contains perindopril erbumine (also known as tert -butylamine). The new formulation contains perindopril arginine; it will be distinguished by new brand names (Coversyl Arginine, Coversyl Arginine Plus) and new packaging. Coversyl 2, 4 and 8mg tablets are equivalent to Coversyl Arginine 2.5, 5 and 10mg. Servier says the change is part of the simplification and harmonisation of global manufacturing; the arginine salt is already used in other countries and offers greater stability and a longer shelf-life. Both Coversyl and Coversyl Arginine will be in the supply chain for the next few weeks. Generic perindopril will continue to be the erbumine salt and prescriptions for generic perindopril are not affected. New from NICE Diabetes in pregnancy: management of diabetes and its complications from preconception to the postnatal period. Clinical Guidance No. 63, March 2008 This clinical guideline focuses on additional aspects of care for women with gestational diabetes (88 per cent of cases) or pre-existing diabetes (of which about 40 per cent is type 2 diabetes) and their babies. To date, insulin aspart (NovoRapid) is the only drug in the guideline specifically licensed for use in pregnancy and NICE advises obtaining informed consent to implement its recommendations for using other insulins and oral hypoglycaemic agents. As with other guidelines, NICE begins by stressing the importance of patient-centred care and involving women in decisions about their treatment. The guideline is divided into six sections, dealing with consecutive periods of pregnancy. Preconceptual planning should include empowering women to help them reduce risks, optimising glycaemic control (after retinal assessment) and increasing monitoring intensity, and providing information about the effects of pregnancy on diabetes. Metformin may be recommended as an adjunct or alternative to insulin, but other oral hypoglycaemic agents should be replaced with insulin, although glibenclamide is an option during pregnancy. Isophane insulin is the preferred long-acting insulin; lispro (Humalog) and aspart are considered safe to use. ACE inhibitors and angiotensin-II receptor blockers should be replaced with other antihypertensive agents and statins should be discontinued. Recommendations for screening and treatment of gestational diabetes build on previous guidance (CG62). Drug treatment will be needed by 10-20 per cent , this includes insulin (soluble, aspart or lispro) and/or metformin or glibenclamide, tailored to individual need. Antenatal care includes optimising glycaemic control. Insulin lispro or aspart should be considered in preference to soluble insulin. If glycaemic control cannot be achieved with insulin injections, an insulin pump may be indicated. The guideline includes a timetable for appointments and the care that should offered after each interval. Recommendations for intrapartum care, which supplement those in CG55, include frequent monitoring of blood glucose. Neonatal care includes recommendations for monitoring and screening the infant and the management of hypoglycaemia. Postnatal care (supplementing CG37) involves adjusting maternal treatment to avoid hypoglycaemia and recommendations for returning to community care. Metformin and glibenclamide are the only oral agents suitable for breastfeeding women. Women with gestational diabetes need advice about glycaemic control and planning for future pregnancies. Lifestyle advice and measurement of annual fasting plasma glucose should be offered. Inhaled corticosteroids for the treatment of chronic asthma in adults and in children aged 12 years and over. Technology Appraisal No. 138, March 2008 The latest technology appraisal of asthma treatments covers inhaled steroids for adults and children over 12 with chronic asthma. It makes only two recommendations. First, the cheapest appropriate option is recommended. Second, when a steroid and a long-acting beta2-agonist are indicated, the decision to prescribe a combined inhaler or separate devices should take into account therapeutic need and likely adherence. Combined inhalers are currently less expensive than separate devices, though they may not remain so. When a combined inhaler is chosen it should be the cheapest. NICE concludes that, at equivalent doses, there is little difference in the effectiveness or adverse event profile of the available steroids or the fixed-dose combinations. According to specialist advice, choosing the best device for an individual remains the overriding concern. Continuous positive airway pressure for the treatment of obstructive sleep apnoea/hypopnoea syndrome. Technology Appraisal No. 139, March 2008 NICE recommends continuous positive airway pressure (CPAP) for adults with moderate or severe obstructive sleep apnoea, and for those with a milder disorder if quality of life and functioning are impaired and alternative strategies such as lifestyle change have failed. Diagnosis and treatment is the responsibility of a specialist team. A CPAP device costs £250-£550 and lasts for seven years. Copyright © 2008 Wiley Interface Ltd [source] Antimicrobial therapy for multidrug resistant pathogensEQUINE VETERINARY EDUCATION, Issue 6 2009J. S. Weese Summary Multidrug resistant bacteria are tremendous causes of morbidity and mortality in human medicine, and emerging pathogens in equine medicine. A variety of organisms, such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus spp. (VRE) and multidrug resistant Acinetobacter spp., Pseudomonas spp. and Enterobacteriaceae are of concern in equine medicine. Veterinary practitioners need to be aware of key diagnostic, clinical, therapeutic, epidemiological and infection control aspects to limit the impact of these organisms on the equine, and perhaps human, population. [source] Intravenous and intratracheal administration of trimetoquinol, a fast-acting short-lived bronchodilator in horses with ,heaves'EQUINE VETERINARY JOURNAL, Issue 6 2006F. C. CAMARGO Summary Reason for performing study: Trimetoquinol (TMQ) is a potent ,-adrenoceptor agonist bronchodilator used in human medicine but has not been evaluated for potential use as a therapeutic agent for horses with ,heaves'. Objectives: To assess the pharmacodynamics of TMQ in horses with ,heaves' to determine potential therapeutic effects. Methods: Increasing doses of TMQ were administered to horses with ,heaves' by i.v. and intratracheal (i.t.) routes. Doses ranged 0.001,0.2 ,g/kg bwt i.v. and 0.01,2 ,g/kg bwt i.t. Cardiac and airways effects were assessed by measurement of heart rate (HR) and maximal change in pleural pressure (,Pplmax), respectively. Side effects of sweating, agitation and muscle trembling were scored subjectively. Duration of action to i.v. (0.2 ,g/kg bwt) and i.t. (2 ,g/kg bwt) TMQ was evaluated over 6 h. Results: Intravenous TMQ was an exceptionally potent cardiac stimulant. Heart rate increased at 0.01 ,g/kg bwt, and was still increasing after administration of highest dose, 0.2 ,g/kg bwt. Airway bronchodilation, measured as a decrease in ,Pplmax, also commenced at 0.01 ,g/kg bwt. By the i.t. route, TMQ was 50,100-fold less potent than by i.v. Side effects included sweating, agitation and muscle trembling. Overall, the onset of HR and bronchodilator effects was rapid, within about 3 min, but effects were over at 2 h. Conclusion: When administered i.v. and i.t., TMQ is a highly potent cardiac stimulant and a modest bronchodilator. It may not be an appropriate pharmacological agent by i.v. and i.t. routes for the alleviation of signs in horses with ,heaves'. Further studies of TMQ by oral and aerosol routes are necessary. Potential relevance: In horses, TMQ is a fast-acting bronchodilator with a short duration of action. It could be used as a rescue agent during an episode of ,heaves'. The i.v. and i.t. administration of TMQ is associated with side effects, similar to those reported for all other ,-agonists. However, other routes, such as aerosol and oral, may prove useful and safe for the alleviation of bronchoconstriction typical of ,heaves'. [source] Assessment of a pyrogallol red technique for total protein measurement in the cerebrospinal fluid of dogsJOURNAL OF SMALL ANIMAL PRACTICE, Issue 12 2003S. Behr The measurement of protein concentration in the cerebrospinal fluid is a basic analytical method in neurology. In this study, a pyrogallol red technique using a human albumin calibrator previously validated in human medicine was tested for canine samples, and the results were compared with those obtained using urine test strips. Pyrogallol red significantly (P<0·05) but moderately underestimated purified dog albumin and globulins. The imprecision of the technique was low: intra- and between-series coefficients of variation were 1·6 and 4·3 per cent at protein concentrations of about 0·3 g/litre. Over 49 samples, there was good agreement between the pyrogallol red and test strip results (r=0·63), especially for low and high protein concentrations, but misclassifications were observed with,+'test strip readings. [source] The ubiquitous role of zinc in health and diseaseJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 3 2009DACVIM, Julia E. Cummings DVM Abstract Objective , To review zinc physiology and pathophysiology and the importance of zinc toxicity and deficiency in veterinary patients. Data Sources , A review of human and veterinary medical literature. Human Data Synthesis , There is a significant amount of original research in humans and animals on the role of zinc in multiple organ systems. There is also significant data available on human patients with zinc abnormalities. Veterinary Data Synthesis , Zinc deficiency has been studied in dogs with genetic disease and dietary deficiency leading to dermatological disease and immune deficiency. Zinc toxicity has been described after ingestion of metallic foreign bodies containing zinc. Conclusions , Historically, the role of zinc in health and disease has been studied through patients with toxicity or severe deficiency with obvious clinical signs. As the ubiquitous contribution of zinc to structure and function in biological systems was discovered, clinically significant but subtle deficiency states have been revealed. In human medicine, mild zinc deficiencies are currently thought to cause chronic metabolic derangement leading to or exacerbating immune deficiency, gastrointestinal problems, endocrine disorders, neurologic dysfunction, cancer, accelerated aging, degenerative disease, and more. Determining the causal relationships between mild zinc deficiency and concurrent disease is complicated by the lack of sensitive or specific tests for zinc deficiency. The prevalence of zinc deficiency and its contribution to disease in veterinary patients is not well known. Continued research is warranted to develop more sensitive and specific tests to assess zinc status, to determine which patients are at risk for deficiency, and to optimize supplementation in health and disease. [source] Apoptosis: A review of pro-apoptotic and anti-apoptotic pathways and dysregulation in diseaseJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 6 2008Mauria A. O'Brien DVM Abstract Objective , To review the human and veterinary literature on the biology of apoptosis in health and disease. Data Sources , Data were examined from the human and veterinary literature identified through Pubmed and references listed in appropriate articles pertaining to apoptosis. Human Data Synthesis , The role of apoptosis in health and disease is a rapidly growing area of research in human medicine. Apoptosis has been identified as a component of human autoimmune diseases, Alzheimer's disease, cancer, and sepsis. Veterinary Data Synthesis , Research data available from the veterinary literature pertaining to apoptosis and its role in diseases of small animal species is still in its infancy. The majority of veterinary studies focus on oncologic therapy. Most of the basic science and human clinical research studies use human blood and tissue samples and murine models. The results from these studies may be applicable to small animal species. Conclusions , Apoptosis is the complex physiologic process of programmed cell death. The pathophysiology of apoptosis and disease is only now being closely evaluated in human medicine. Knowledge of the physiologic mechanisms by which tissues regulate their size and composition is leading researchers to investigate the role of apoptosis in human diseases such as cancer, autoimmune disease and sepsis. Because it is a multifaceted process, apoptosis is difficult to target or manipulate therapeutically. Future studies may reveal methods to regulate or manipulate apoptosis and improve patient outcome. [source] Use of dopamine in acute renal failureJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 2 2007DACVECC, Nadja E. Sigrist DrMedVet Abstract Objective: To review the current understanding of dopamine and its use in the prevention and treatment of acute renal failure (ARF). Data sources: Original research articles and scientific reviews. Human data synthesis: Low-dose dopamine administration has been shown to increase natriuresis and urinary output in both healthy individuals and in a few small studies in human patients with renal insufficiency. However, in several large meta-analyses, dopamine treatment did not change mortality or the need for dialysis. Due to the potential side effects, the use of dopamine for prevention and treatment of ARF is no longer recommended in human medicine. Veterinary data synthesis: Low-dose dopamine increases urinary output in healthy animals and animal models of ARF if given before the insult. There are no available studies looking at the effect of low-dose dopamine therapy in naturally occurring ARF in dogs or cats. Conclusion: Due to the potential side effects of low-dose dopamine therapy, the results from large human trials, and the lack of information in veterinary medicine, the use of dopamine for treatment of ARF in veterinary patients should be further evaluated. [source] Nosocomial infections and antimicrobial resistance in critical care medicineJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 1 2006Jennifer S. Ogeer-Gyles DVM Abstract Objective: To review the human and companion animal veterinary literature on nosocomial infections and antimicrobial drug resistance as they pertain to the critically ill patient. Data sources: Data from human and veterinary sources were reviewed using PubMed and CAB. Human data synthesis: There is a large amount of published data on nosocomially-acquired bloodstream infections, pneumonia, urinary tract infections and surgical site infections, and strategies to minimize the frequency of these infections, in human medicine. Nosocomial infections caused by multi-drug-resistant (MDR) pathogens are a leading cause of increased patient morbidity and mortality, medical treatment costs, and prolonged hospital stay. Epidemiology and risk factor analyses have shown that the major risk factor for the development of antimicrobial resistance in critically ill human patients is heavy antibiotic usage. Veterinary data synthesis: There is a paucity of information on the development of antimicrobial drug resistance and nosocomially-acquired infections in critically ill small animal veterinary patients. Mechanisms of antimicrobial drug resistance are universal, although the selection effects created by antibiotic usage may be less significant in veterinary patients. Future studies on the development of antimicrobial drug resistance in critically ill animals may benefit from research that has been conducted in humans. Conclusions: Antimicrobial use in critically ill patients selects for antimicrobial drug resistance and MDR nosocomial pathogens. The choice of antimicrobials should be prudent and based on regular surveillance studies and accurate microbiological diagnostics. Antimicrobial drug resistance is becoming an increasing problem in veterinary medicine, particularly in the critical care setting, and institution-specific strategies should be developed to prevent the emergence of MDR infections. The collation of data from tertiary-care veterinary hospitals may identify trends in antimicrobial drug resistance patterns in nosocomial pathogens and aid in formulating guidelines for antimicrobial use. [source] Intermittent and Continuous Enteral Nutrition in Critically Ill Dogs: A Prospective Randomized TrialJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2010M. Holahan Background: Malnutrition is a common problem in critically ill dogs and is associated with increased morbidity and mortality in human medicine. Enteral nutrition (EN) delivery methods have been evaluated in humans to determine which is most effective in achieving caloric goals. Objectives: To compare continuous infusion and intermittent bolus feeding of EN in dogs admitted to a critical care unit. Animals: Fifty-four dogs admitted to the critical care unit and requiring nutritional support with a nasoenteric feeding tube. Methods: Prospective randomized clinical trial. Dogs were randomized to receive either continuous infusion (Group C) or intermittent bolus feeding (Group I) of liquid EN. The percentage of prescribed nutrition delivered (PPND) was calculated every 24 hours. Frequencies of gastrointestinal (GI), mechanical, and technical complications were recorded and gastric residual volumes (GRVs) were measured. Results: PPND was significantly lower in Group C (98.4%) than Group I (100%). There was no significant difference in GI or mechanical complications, although Group C had a significantly higher rate of technical complications. GRVs did not differ significantly between Group C (3.1 mL/kg) and Group I (6.3 mL/kg) and were not correlated with the incidence of vomiting or regurgitation. Conclusions and Clinical Importance: There was a statistically significant difference in the PPND between continuously and intermittently fed dogs, but this difference is unlikely to be clinically relevant. Critically ill dogs can be successfully supported with either continuous infusion or intermittent bolus feeding of EN with few complications. Increased GRVs may not warrant termination of enteral feeding. [source] Placebo Effect in Canine Epilepsy TrialsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2010K.R. Muñana Background: The placebo effect is a well-recognized phenomenon in human medicine; in contrast, little information exists on the effect of placebo administration in veterinary patients. Hypothesis: Nonpharmacologic therapeutic effects play a role in response rates identified in canine epilepsy trials. Animals: Thirty-four dogs with epilepsy. Methods: Meta-analysis of the 3 known prospective, placebo-controlled canine epilepsy trials. The number of seizures per week was compiled for each dog throughout their participation in the trial. Log-linear models were developed to evaluate seizure frequency during treatment and placebo relative to baseline. Results: Twenty-two of 28 (79%) dogs in the study that received placebo demonstrated a decrease in seizure frequency compared with baseline, and 8 (29%) could be considered responders, with a 50% or greater reduction in seizures. For the 3 trials evaluated, the average reduction in seizures during placebo administration relative to baseline was 26% (P= .0018), 29% (P= .17), and 46% (P= .01). Conclusions and Clinical Importance: A positive response to placebo administration, manifesting as a decrease in seizure frequency, can be observed in epileptic dogs. This is of importance when evaluating open label studies in dogs that aim to assess efficacy of antiepileptic drugs, as the reported results might be overstated. Findings from this study highlight the need for more placebo-controlled trials in veterinary medicine. [source] Role of Lung Surfactant in Respiratory Disease: Current Knowledge in Large Animal MedicineJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 2 2009U. Christmann Lung surfactant is produced by type II alveolar cells as a mixture of phospholipids, surfactant proteins, and neutral lipids. Surfactant lowers alveolar surface tension and is crucial for the prevention of alveolar collapse. In addition, surfactant contributes to smaller airway patency and improves mucociliary clearance. Surfactant-specific proteins are part of the innate immune defense mechanisms of the lung. Lung surfactant alterations have been described in a number of respiratory diseases. Surfactant deficiency (quantitative deficit of surfactant) in premature animals causes neonatal respiratory distress syndrome. Surfactant dysfunction (qualitative changes in surfactant) has been implicated in the pathophysiology of acute respiratory distress syndrome and asthma. Analysis of surfactant from amniotic fluid allows assessment of fetal lung maturity (FLM) in the human fetus and exogenous surfactant replacement therapy is part of the standard care in premature human infants. In contrast to human medicine, use and success of FLM testing or surfactant replacement therapy remain limited in veterinary medicine. Lung surfactant has been studied in large animal models of human disease. However, only a few reports exist on lung surfactant alterations in naturally occurring respiratory disease in large animals. This article gives a general review on the role of lung surfactant in respiratory disease followed by an overview of our current knowledge on surfactant in large animal veterinary medicine. [source] Use of Electrohydraulic Lithotripsy in 28 Dogs with Bladder and Urethral CalculiJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 6 2008A. Defarges Background: Electrohydraulic lithotripsy (EHL) has been used as an alternative to cystotomy in human medicine to remove urinary calculi. This prospective study evaluated the efficacy and safety of EHL to remove urinary calculi in dogs. Hypothesis: EHL is an efficient and safe method of treatment of bladder and urethral calculi in dogs. Methods: Dogs presented between January 1, 2005 and June 1, 2007 with lower urinary tract calculi diagnosed by radiographs or ultrasound examination were included in the study. Physical examination, CBC, biochemistry, urinalysis, and urine culture were performed at presentation. EHL and voiding urohydropulsion were performed under general anesthesia. Patients received IV fluids for 12 hours after which they were rechecked by ultrasound examination and discharged with antibiotics and anti-inflammatory drugs for 5 days. All patients were reevaluated 1, 3, and 6 months after presentation by physical examination, urinalysis, and ultrasonography. Results: Twenty-eight dogs (19 males, 9 females) presented with bladder or urethral calculi or both underwent lithotripsy. Their median weight was 8.3 kg. Calcium oxalate calculi were present in 22 dogs, struvite in 4, and mixed calculi in 2. Fragmentation was done in the bladder (23 dogs) and in the urethra (12 dogs). Calculus-free rate was higher for urethral than for bladder calculi in males and higher for bladder calculi in females than in males. No major complications were reported. Twelve dogs relapsed within 6 months. Conclusions: Results of this study support the use of EHL as a minimally invasive treatment for bladder calculi in females and for urethral calculi in male dogs. [source] Thyroid Imaging in the Dog: Current Status and Future DirectionsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 4 2007O. Taeymans This review describes the advantages and disadvantages of radiography, ultrasonography, and nuclear medicine in the 2 most frequent thyroid pathologies of the dog: acquired primary hypothyroidism and thyroid neoplasia. Ultrasonography and scintigraphy remain the 2 most indicated imaging modalities for these thyroid abnormalities. However, as in human medicine, computed tomography and magnetic resonance imaging also have potential indications. This is especially the case in the evaluation of the extent, local invasiveness, and local or distant metastases of thyroid neoplasia. Based on experience with different imaging modalities in people, we suggest future directions in the imaging of the canine thyroid gland. [source] Reflection paper on the use of third and fourth generation cephalosporins in food producing animals in the European Union: development of resistance and impact on human and animal healthJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2009Scientific Advisory Group on Antimicrobials of the Committee for Medicinal Products for Veterinary Use Resistance to third and fourth generation cephalosporins is rapidly increasing in bacteria infecting humans. Although many of these problems are linked to human to human transmission and to use of antimicrobials in human medicine, the potential role of community reservoirs such as food producing animals needs to be scrutinized. Resistance to third and fourth generation cephalosporins is emerging in enteric bacteria of food producing animals and also in food of animal origin. The genes encoding resistance to these cephalosporins are transferrable and often linked to other resistance genes. Systemic use of third and fourth cephalosporins selects for resistance, but co-selection by other antimicrobials is also likely to influence prevalence of resistance. Although there are many uncertainties, the potential consequences of a further increase of resistance to this critically important class of antimicrobials in bacteria colonising animals are serious. Measures to counter a further increase and spread of resistance among animals should therefore be considered. [source] Pharmacokinetics of the injectable formulation of methadone hydrochloride administered orally in horsesJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009R. L. LINARDI Methadone hydrochloride is a synthetic ,-opioid receptor agonist with potent analgesic properties. Oral methadone has been successfully used in human medicine and may overcome some limitations of other analgesics in equine species for producing analgesia with minimal adverse effects. However, there are no studies describing the pharmacokinetics (PK) of oral opioids in horses. The aim of this study was to describe the PK of orally administered methadone (0.1, 0.2 and 0.4 mg/kg) and physical effects in 12 healthy adult horses. Serum methadone concentrations were measured by gas chromatography/mass spectrometry at predetermined time points for 24 h, and PK parameters were estimated using a noncompartmental model. Physical effects were observed and recorded by experienced clinicians. No drug toxicity, behavioural or adverse effects were observed in the horses. The disposition of methadone followed first order elimination and a biphasic serum profile with rapid absorption and elimination phases. The PK profile of methadone was characterized by high clearance (Cl/F), small volume of distribution (Vd/F) and short elimination half-life (t1/2). The mean of the estimated t1/2 (SD) for each dose (0.1, 0.2 and 0.4 mg/kg) was 2.2 (35.6), 1.3 (46.1) and 1.5 (40.8), and the mean for the estimated Cmax (SD) was 33.9 (6.7), 127.9 (36.0) and 193.5 (65.8) respectively. [source] Pharmacological approaches towards rationalizing the use of endoparasitic drugs in small animalsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2006S. F. SANCHEZ BRUNI Parasitic diseases are an important health concern to small animal veterinarians worldwide, and their zoonotic potential is also of relevance to human medicine. The treatment and control of such conditions relies heavily on pharmaceutical intervention using a range of antiparasitic drugs and/or their biologically active metabolites. Broad spectrum agents have been produced, although narrow and even monospecific drugs are used in some situations. Their efficacy may depend on dosage, the target pathogen(s), the host species and/or the site of infection. Optimal use of antiparasitics requires a detailed consideration of the pharmacokinetic and pharmacodynamic properties of the drugs in specific clinical contexts. This review summarizes the present status of knowledge on the metabolism, and physicochemical and pharmacological properties of the major antiparasitic drugs currently used in small animal veterinary practice. In addition, data relevant to therapeutic dosage, efficacy and clinical indication/contraindication, particularly in relation to combination drug therapy, are included. [source] Antimicrobial resistance in livestockJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2003B. Catry Antimicrobial resistance may become a major problem in veterinary medicine as a consequence of the intensive use and misuse of antimicrobial drugs. Related problems are now arising in human medicine, such as the appearance of multi-resistant food-borne pathogens. Product characteristics, dose, treatment interval and duration of treatment influence the selection pressure for antimicrobial drug resistance. There are theoretical, experimental and clinical indications that the emergence of de novo resistance in a pathogenic population can be prevented by minimizing the time that suboptimal drug levels are present in the infected tissue compartment. Until recently, attention has been focused on target pathogens. However, it should be kept in mind that when antimicrobial drugs are used in an individual, resistance selection mainly affects the normal body flora. In the long term, this is at least equally important as resistance selection in the target pathogens, as the horizontal transfer of resistance genes converts almost all pathogenic bacteria into potential recipients for antimicrobial resistance. Other factors contributing to the epidemiology of antimicrobial resistance are the localization and size of the microbial population, and the age, immunity and contact intensity of the host. In livestock, dynamic herd-related resistance patterns have been observed in different animal species. [source] The Development of the Metanephric Kidney in the PigANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 2005H. Bragulla Aims:, The metanephric kidneys of the pig are used as xenotransplants in human medicine. In order for transplants to fit within the host organisms, the subcapsular blastema and blood vessels are crucial for the development of new nephrons to sustain the organ functions. The aim of this study is to obtain data concerning the post-natal development of metanephric nephrons in the porcine kidney. Materials and Methods:, The metanephric kidneys of six porcine fetuses with a crown-rump length ranging from 40 mm to 220 mm of eight piglets aged between 6 to 10 weeks and of three adult pigs were studied. Eight lectins as well as anti-actin and anti-myosin antibodies were used for lectin- and immunohistochemistry to study the subcapsular metanephric blastema, to visualize the blood-urine barrier in the nephrons and collecting tubules, and to study the blood vessels in both the renal cortex and marrow. Results and Conclusions:, A subcapsular metanephric blastema was still present in the kidney of 10-week-old piglets. Dense condensation of mesenchymal cells surrounded the terminal branches of the collecting ducts and showed first signs of mesenchymal-epithelial transformation. Characteristic comma-shaped and s-shaped bodies were found in and underneath the subcapsular blastema. In the fibrous renal capsule of six-week-old piglets, a first faint binding reaction of anti-actin was visible and intensified in the fibrous renal capsule in ten-week-old piglets and in adult pigs. In addition, the smooth-muscle layers of the blood vessels were stained by the anti-actin and anti-myosin antibodies. The lectins showed various affinities to the endothelium of blood vessels and to the epithelial cells lining of the capsules of the metanephric renal corpuscles, the various parts of the renal tubules, as well as the collecting tubules and the renal pelvis. The affinity of the epithelial cells to a specific lectin varies in neighbouring cells, indicating different cell activities or cell cycles. [source] Computed Tomography of the Lungs of the Dog by a Six-generation CT Scanner, Intravenous Contrast Medium and Different WindowsANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 2005L. Cardoso Computed tomography (CT) is a modern technique of image diagnosis particularly recommended in human medicine to evaluate the existence of pulmonary pathological changes such as neoplasms, metastasis, interstitial infiltrates, etc. In veterinary medicine, however, few anatomical and clinical CT studies in the dog have used apparatus of the latest generation, including injection of intravenous contrast and application of regional specific CT windows with different window width (WW) and window level (WL) to evaluate the lungs, the pulmonary vessels and the bronchial structures. This methodology allows the obtaining of clear CT images with high capacity of tissue discrimination and different shades of attenuation. In this work we have planned a tomographic study of the lungs of the dog by using a six-generation spiral CT scanner (Toshiba Ex Vision), belonging to the private Medical Institute of Radiology ,Irion' of Porto Alegre, Brazil. Four mixed-breed mature dogs (4,6 years, 15,20 kg) were used, two males and two females. The dogs were anaesthetized and kept in a maximum inspiration when obtaining the images. Dogs were placed in a stretcher in a ventral or sternal recumbency. Previously, the contrast urografin® was injected in the cephalic vein. Different CT windows were applied in order to increase the quality of the images: pulmonary window (WW 928; WL -680), high-resolution pulmonary window (WW 1085; WL -750), and soft tissue window (WW 652; WL -34). The use of intravenous contrast, different CT windows and a modern CT apparatus produced excellent images of the pulmonary parenchyma, the pleural cavity, the pulmonary veins, the lobular rami of the pulmonary artery and the lobular bronchi. [source] Stereology of the Liver in Three Species of Leontopithecus (Lesson, 1840) Callitrichidae , PrimatesANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 3 2004C. H. F. Burity Summary Studies on liver morphology and stereology are relevant to the comparative anatomical and pathological research. They also facilitate the use of non-human primates in basic research, which has substantially supported studies in human medicine. Quantitative studies of liver structures have also been more extensive in Old World primates and other vertebrates. Twenty-three livers of adult lion tamarins were studied (six Leontopithecus rosalia, seven Leontopithecus chrysomelas, and 10 Leontopithecus chrysopygus), dissected, and fixed in 10% neutral buffered formalin solution. For stereological quantification, the liver was regarded as consisting of parenchyma (hepatocytes) and stroma (non-hepatocytes). The volume density (Vv) was determined by point counting, and the disector method was used to obtain the numerical density of hepatocytes (Nv). Hepatic stereological differences among the three species of lion tamarins were not statistically significant. Therefore, the pooled Vv[hepatocyte] and Vv[stroma] could be determined as 96.2 and 7.4%, respectively, and Nv[hepatocyte] as 500.33 × 106 cm,3 . Significantly different, the values found for Vv[hepatocyte] and Nv[hepatocyte] in lion tamarins were, respectively, 0.09 and 2.8 times greater than those in baboons, and 0.17 and 3.8 times greater than those in man. However, the Vv[stroma] was 1.04 times smaller than that in baboons and 1.79 times smaller than that in man. [source] The taming of the shrew or corneal transplantation: past, present and futureACTA OPHTHALMOLOGICA, Issue 2008U PLEYER Keratoplasty has definitely its paradoxes. It has been the first successful transplantation in man and is with approx. 100. 000 grafts/year easily the most frequent allograft in human medicine. At the same time it is still the least understood form of transplantation in respect to its biology. It is both, the most successfull as well as probably the most underestimated procedure regarding its risks in clinical transplantation. Indeed, the common assumtion, that corneal transplantation is a safe procedure with good prognosis may have hindered more intensive effort of research in this field. This lecture aims to highlight significant milestones in the rich history of corneal transplantation, and to pay tribute to the many inspired and dedicated individuals involved in the development of keratoplasty. There are still limitations to corneal transplantation, and corneal allograft rejection still poses the greatest challenge to the modern corneal surgeon. Therefore, particular emphasis will be paid to recent efforts and developments to overcome this challenge. [source] | |||||||||||||||||||||||||